The present invention is drawn to a new diagnosis method for detecting the extend of a inflammatory, fibrotic or cancerous disease in a patient, in particular liver fibrosis, in particular in a patient-infected with hepatitis C virus, by using the serum concentration of easily detectable biological markers. The invention is also drawn to diagnosis kits for the implementation of the method.
Liver biopsy is considered as mandatory for the management of patients infected by the hepatitis C virus (HCV), particularly for the staging of fibrosis (1-4). For patients and general practitioner it can be considered as an aggressive procedure (5-6). Numerous studies have shown significant predictive values of several markers for the diagnosis of cirrhosis (6-15) but none for the diagnosis of earlier stage as few septa (beginning of bridging fibrosis), prospectively in a large population infected only by HCV virus.
It is nevertheless important to be able to detect these early stages in the development of liver pathology, in order to improve the patient treatment, and the follow-up of the disease. As liver biopsy is still an invasive procedure, it could be advantageous to have a fast and easy to perform test that would give a good predictive value of the level of fibrosis in the patient.
After infection by the hepatitis C virus, the evolution of the disease can lead to fibrosis, and later to cirrhosis. The liver biopsy allows for the determination of the stage of the fibrosis, but also the presence of liver necroinflammatory lesions. The intensity and activity of such lesions, in complement to the degree of fibrosis, are acknowledged by physicians as an important factor for diagnosis and prognosis of the evolution of the disease, and in order to determine the type of treatment to administrate.
There is therefore a need to develop a diagnosis method that would give a good predictive value of the presence (or the absence) of fibrosis and/or lesions in a patient, and that would be reliable enough to reduce the need of liver biopsy.
The present invention provides a method of diagnosis that assesses prospectively the predictive value of a combination of simple serum biochemical markers for the diagnosis of an inflammatory, fibrotic or cancerous disease, in particular in the liver of a patient where it is well suited for diagnosis of significant fibrosis (from few septa to cirrhosis) and/or liver necroinflammatory lesions. With the reach of high positive predictive values (prediction of significant fibrosis) or negative predictive values, the number of biopsy indications could be reduced. This could be useful for patients and society in order to reduce the cost and the risk of biopsies especially liver biopsies (6).